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Nature Research, Scientific Reports, 1(1), 2011

DOI: 10.1038/srep00063

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Activation of nitrofurazone by azoreductases: multiple activities in one enzyme

Journal article published in 2011 by Ali Ryan, Elise Kaplan ORCID, Nicola Laurieri, Edward Lowe, Edith Sim
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Azoreductases are well known for azo pro-drug activation by gut flora. We show that azoreductases have a wider role in drug metabolism than previously thought as they can also reduce and hence activate nitrofurazone. Nitrofurazone, a nitroaromatic drug, is a broad spectrum antibiotic which has until now been considered as activated in bacteria by nitroreductases. The structure of the azoreductase with nitrofurazone bound was solved at 2.08 Å and shows nitrofurazone in an active conformation. Based on the structural information, the kinetics and stoichiometry of nitrofurazone reduction by azoreductase from P. aeruginosa, we propose a mechanism of activation which accounts for the ability of azoreductases to reduce both azo and nitroaromatic drugs. This mode of activation can explain the cytotoxic side-effects of nitrofurazone through human azoreductase homologues.